Classical CRISPR screens enable comprehensive gene function analyses in vitro. Their meaningfulness is nevertheless limited, as they do not fully re ject the complexity of living organisms. Reliable and reproducible in vivo screening often fails, because the effects of genetic changes are very weak due to insuf ficient representation of the transduced sgRNAs. These meagre effects are further eclipsed by additional internal and external interferences and clonal distortions.
The CRISPR-StAR technology developed by Dr Ulrich Elling and his team at the IMBA – Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna has overcome this obstacle. It is based on Cre-inducible expression vectors and single-cell barcoding for the sgRNAs used in CRISPR screens. Data published in Nature Biotechnology show that precise and controlled gene editing is possible, guaranteeing a definite distinction between apparent and real genetic hits. ‘This enables us to gain reliable insights into the genetic dependencies underlying therapeutic challenges such as therapy-resistant melanoma,’ explains Ulrich Elling.
With support from Ascenion, the technology has been licensed to the US company ViVerita Therapeutics. The focus is on identifying new target structures for cancer therapy. ViVerita’s Vienna subsidiary, headed by Ulrich Elling, also provides technological expertise and services to biopharmaceutical partners. ‘Our aim is to fully exploit the potential of this technology for the development of innovative therapies,’ says Dr Elling.
(Annual Review 2024/25)